The overall goal of this project is to determine how the output of the main olfactory bulb regulated by is the local circuitry of this structure. In particular, this proposal focuses on studying lateral inhibition, a ubiquitous feature of neuronal circuits thought to play a central role in determining the specificity of stimulus-evoked responses and in regulating network dynamics in many brain regions, including the olfactory bulb. Gaining a better understanding of functional properties of neural circuitry such as lateral inhibition is of central importance to many areas of neuroscience and the olfactory bulb presents an interesting and tractable model system in which to study fundamental questions about the regulation of neural activity by circuitry. These experiments are designed to address the hypothesis that one function of inhibitory circuitry connecting principal neurons associated with different glomerular modules in the olfactory bulb is to mediate a functional lateral inhibition. Specifically we use paired recordings from mitral cells to study the properties of synaptic circuits making functional connections between mitral cells associated with different glomeruli. Using this approach we will test whether lateral inhibition between pairs of individual mitral cells occurs when mitral cell activity is similar in frequency to what has been reported from in vivo recordings made during odor stimulation. We also will investigate short- term plasticity of lateral inhibitory connections, and study the interaction of recurrent and lateral inhibition. In conjunction these results will provide important insights into the role played by inhibitory circuits in shaping sensory representations, especially in the olfactory bulb and in understanding how abnormalities of inhibition can lead to functional deficits in the olfactory bulb and other brain networks.